The mammalian lung contains a number of cell types and subtypes surrounded and supported by extracellular matrices, either interstitial or basement membrane in nature. Such matrices contain collagen, elastin, proteoglycans, fibronectin, and other macromolecular components; the integrity of the matrix is thought to account for many of the mechanical properties of lung. In pulmonary diseases, the matrix is often prominently affected. For example, in emphysema, derangement of elastin occurs so that it is morphologically abnormal; type II cell proliferation and differentiation may be influenced by exposed basement membranes during lung repair. We propose to address questions of matrix production and cell-matrix interactions in normal and fibrotic lung, using a cell culture approach. Three major protocols are: 1) to elucidate, in detail, the biogenesis of matrix macromolecules as a function of chronologic age, from embryonic lung to senescent lung; the appearance and temporal sequence of specific marcomolecules elaborated by lung fibroblasts will be quantitatively assayed; 2) to develop pure populations of type II alveolar cells, endothelial cells from capillary (alveolar) regions and pulmonary artery, and to define the abilities of these cells to maintain their differentiated state on preformed matrices, as well as the capability of the cells to produce specific matrix components; the ability of specific cell membrane components to recognize matrix molecules. These studies will rely upon development of monoclonal antibodies for specific cell selection and for cell-matrix interactions; 3) to study the effects of disease processes upon control of lung cell proliferation and production of matrix components; the role of factors elaborated by mononuclear cells of fibrotic lung in regulating matrix production of pure cell populations will be examined, using co-culture or conditioned media. This integrated approach should help define the relationships between certain alveolar cell types and their supporting extracellular matrix, both in normal lung and in a model of pulmonary fibrosis. Insights into the cell-matrix interactions may be forthcoming when reagents such as monoclonal antibodies are used to dissect the cells from the matrix with the aim of identifying specific cell membrane binding sites, similar to those described in non-pulmonary tissues.